5-111367789-A-G

Variant names:

• chr5-111367789-A-G
• rs3756612
• NM_001744.6:c.241-7061A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001744.6(CAMK4):​c.241-7061A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,076 control chromosomes in the GnomAD database, including 2,524 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2524 hom., cov: 31)
• Consequence: CAMK4 NM_001744.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.629
• Publications: 3 publications found

Genes affected

CAMK4 (HGNC:1464): (calcium/calmodulin dependent protein kinase IV) The product of this gene belongs to the serine/threonine protein kinase family, and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. This enzyme is a multifunctional serine/threonine protein kinase with limited tissue distribution, that has been implicated in transcriptional regulation in lymphocytes, neurons and male germ cells. [provided by RefSeq, Jul 2008]

CAMK4 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Illumina

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK4	NM_001744.6	c.241-7061A>G		intron_variant	Intron 2 of 10	ENST00000282356.9	NP_001735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMK4	ENST00000282356.9	c.241-7061A>G		intron_variant	Intron 2 of 10	1	NM_001744.6	ENSP00000282356.4

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24926 AN: 151958 Hom.: 2521 Cov.: 31

Gnomad AFR AF: 0.0455

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.166

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.164 AC: 24928 AN: 152076 Hom.: 2524 Cov.: 31 AF XY: 0.168 AC XY: 12505 AN XY: 74308

African (AFR) AF: 0.0454 AC: 1887 AN: 41552

American (AMR) AF: 0.232 AC: 3533 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 512 AN: 3468

East Asian (EAS) AF: 0.235 AC: 1209 AN: 5142

South Asian (SAS) AF: 0.255 AC: 1227 AN: 4820

European-Finnish (FIN) AF: 0.224 AC: 2368 AN: 10566

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13704 AN: 67968

Other (OTH) AF: 0.169 AC: 357 AN: 2108

Alfa AF: 0.176 Hom.: 2702

Bravo AF: 0.158

Asia WGS AF: 0.258 AC: 897 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.9
DANN	Benign	0.54
PhyloP100		0.63
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3756612; hg19: chr5-110703487; COSMIC: COSV56682479; COSMIC: COSV56682479;